Silvia Pavone

Pathological changes caused by Anoplocephala perfoliata in the mucosa/submucosa and in the enteric nervous system of equine ileocecal junction

In this study, pathological changes caused by Anoplocephala perfoliata in the ileocecal junction were investigated in 31 regularly slaughtered mixed-breed horses of both sexes. Our results showed a significant relationship between parasite burden and grading of histopathological lesions in the mucosa and submucosa. Hypertrophy of the circular muscle layer was found in infected horses. Moreover, enteric nervous system evaluation showed a significant injury of intestinal nervous elements in the horses with moderate to high parasitism expressed as an increase of degenerative-regressive changes in neuronal cells and a decrease in the number of myenteric ganglia and neuronal cells. These findings can help to clarify the pathogenesis of intestinal motility disorders associated with A. perfoliata infection in horses.

Oncolytic activity of Avian influenza virus in human pancreatic ductal adenocarcinoma cell lines.

ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3- and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCE Despite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These results suggest that slightly pathogenic IAVs may prove to be effective for oncolytic virotherapy of PDA and provide grounds for further studies to develop specific and targeted viruses, with the aim of testing their efficacy in clinical contexts.

Histological and immunohistochemical studies of changes in myenteric plexuses and in interstitial cells of Cajal associated with equine colic.

In this study we investigated the histological changes of the myenteric plexuses and interstitial cells of Cajal (ICC) in gut samples from horses with colic to try to find results useful in the prognostic evaluation of enteric lesions. A morphologic and quantitative study of myenteric ganglia, ganglion cells and neuronal chromatolytic and necrotic changes of 24 horses with colic was performed. For ganglion cells, enteroglial cells and ICC immunolabeling was also performed to identify cell functional disorders. A significant increase of neuronal chromatolysis and necrosis occurred in horses suffering from colic throughout the gut. The neuron-specific enolase (NSE) and synaptophysin immunoreaction quantified with image analysis showed a significant loss of neuronal activity in all intestinal tracts of the animals under study associated with a significant loss of ICC immunoreactivity. The results supports immunohistochemical evaluation of ENS and ICC as a useful tool along with morphometric investigations in the evaluation of gut lesions produced during colic syndrome.

Extensive Myenteric Ganglionitis in a Case of Equine Chronic Intestinal Pseudo-obstruction Associated with EHV-1 Infection

A 7-year-old male trotter horse with a history of recurrent colic displayed clinical findings consistent with chronic intestinal pseudo-obstruction (CIP). At laparotomy, an impaction of the descending colon associated with marked atrophy of the right dorsal colon was found. The horse was humanely destroyed and tissues collected at necropsy examination revealed diffuse enteric ganglionitis comprising an infiltrate of CD3(+) T lymphocytes and plasma cells. At all levels of the intestinal tract the number of myenteric ganglia and of normal ganglion cells was decreased significantly. There were chromatolytic or necrotic neurons and the amount of connective tissue surrounding ganglia was increased. Immunohistochemical studies demonstrated slightly reduced expression of neuron-specific enolase and a moderate increase in expression of S100 and glial fibrillary acidic protein in a sample of right dorsal colon taken during the necropsy examination compared with a biopsy sample taken from the same location. Immunolabelling and semi-nested polymerase chain reaction for equine herpesvirus (EHV)-1 performed on the gut were positive, supporting an aetiological relationship between EHV-1 infection and the enteric ganglionitis.

Pathological changes caused by Anoplocephala perfoliata in the equine ileocecal junction

Gastrointestinal motility disorders represent a significant cause of morbidity and mortality in horses. Previously regarded as a non-pathogenic tapeworm, Anoplocephala perfoliata has been recently associated with equine colic. In this study, pathological changes related to A. perfoliata at the ileocecal junction were investigated in 31 slaughtered horses. Our results showed a significant relationship between parasitic burden and grading of histopathological lesions in both the mucosa and submucosa. Moreover, in infested horses, hypertrophy of the circular muscle layer was determined. Finally, an enteric nervous system (ENS) evaluation showed injury to intestinal nervous elements in horses with moderate to high parasitism. In summary, our results on the ENS support a correlation between colic and A. perfoliata infestion in the horse.

Thalamic astrocytic hamartoma and associated meningoangiomatosis in a German shepherd dog

The present paper describes an astrocytic thalamic hamartoma associated with tectal meningoangiomatosis in a 3-month-old female German shepherd dog showing strabismus, opistotonus, circling, and fore limb hypermetria. MR images of the brain showed a well-defined intra-axial mass in the tectal region. The mass was hypointense to gray matter on T2-weighted images and hyperintense to gray matter on precontrast T1-weighted images. Histologically, glial cells arranged in a multinodular pattern characterized the mass. More caudally the lesion merged with subpial abnormal newly formed plaque-like shaped tissue characterized by thick branching bundles of spindle-shaped cells surrounding a central vessel. In the nodules, GFAP and vimentin were diffusely expressed. In the vascular proliferation Factor VIII-positive reaction was limited to endothelial cells while the remaining spindle-shaped cells were diffusely SMA-positive. The glial nodules did not express lysozyme and MAC387, nor neurofilaments and nestin.

Canine Pancreatic Clear Acinar Cell Carcinoma Showing an Unusual Mucinous Differentiation

A small solitary pancreatic nodule was identified in a 10-year-old mixed breed male dog. Microscopically, the lesion consisted of neoplastic clear acinar cells with diffuse, marked mucin production. Immunohistochemical and ultrastructural investigations confirmed the exocrine acinar origin of the tumour. The tumour was classified as a pancreatic clear acinar cell carcinoma (ACC) showing an unusual mucinous differentiation.